This program project focuses on potential methods of optimizing function and facilitating repair in the damaged heart. Approaches include iNOS gene therapy, stem cell (with NO), Gene therapy to LVADS and cell specific gene therapy for iNOS. The faculty and staff of the Imaging core have had a long term and extensive collaborative publication record with the leaders of each project both using conventional and advanced imaging techniques, publishing over 20 articles with project leaders during the last funding period. The studies proposed in this application will rely on a variety of cutting edge microscopic methods. Therefore a central imaging core is defined as an integral component of this proposal for example the core has been using imaging tools to study the biology of NO with project leaders and members since the first reported studies of the importance of the molecule in cell and system physiology, the core has also been involved in imaging the success and efficacy of gene therapy since the first application of the technique. The Core will be housed in the Center for Biologic Imaging (CBI) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this program project. We feel that this combination of core functions will maximize core productivity. The principal roles of the core will be various. We will quantify gene delivery, expression and phenotypic change in tissue, we will track cells following delivery to tissue, we will determine structural change in blood vessels and in cardiac tissue. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle qualitative changes. This core will be used extensively by all projects, though the imaging tools used will vary from project to project.